Compounds of the cyclopentanopolyhydrophenanthrene series and process of preparing them



Patented Dec. 9, 1 941 UNITED STATES PATENT OFFICE COMPOUNDS OF THE CYCLOPENTANOPOLY- HYDROPHENANTHRENE SERIES AND PROCESS OF PREPARING THEM No Drawing. Application February 26, 1941, Se-

rial No. 380,598. In Germany January 31,

4 Claims. (Cl. 260-3971) The present invention relates to compounds of acid radical and the products obtained are subthe cyclopentanopolyhydrophenanthrene series jected to a ketonic cleavage. and to a process of preparing compounds of the By condensing for instance pregnenolone with cyclopentanopolyhydrophenanthrene series. oxalic ester for instance in the presence of sodium U. S. patent application Serial No. 216,470 filed 5 ethylate, the corresponding oxalacetic ester com- June 29, 1938, in the name of Max Bockmiihl, pound is obtained. By subjecting the latter be- Gustav Ehrhart, Heinrich Ruschig and Walter fore or still better after the saponification to a Aumiiller relates to a process of preparing comcarbon monoxide cleavage, for instance by the pounds of the cyclopentanopolyhydrophenanaction of oxidizing agents, such as lead tetrathrene series with a hydroxy ketone group in 17- 10 cylates or aryl iodosoacylates, in the presence of position of the fundamental carbon skeleton an alcohol, for instance ethyl-alcohol, methylwhich consists in treating the corresponding kealcohol or propylalcohol, the ester of the corretones which are free from hydroxy with an sponding malonyl compound is obtained which acylate of the tetravalent lead. at the methylene group now very readily takes up Now we have found that the hydroxy ketone 15 a free or an acylated hydroxyl by suitable oxidizcompounds of the cyclopentanopolyhydrophenaning agents, such as lead tetracylates or aryl threne series may likewise be obtained as follows: iodosoacylates. The carboxyl group situated at there is started from the cyclopentanopolyhydrothe hydroxymethylene group may very readily be phenanthrene compounds having an acyl group removed by heating or by saponification and in l7-position of the carbon skeleton, an acid 20 heating. In the two afore-named reactions the organic radical, such as -COCH3, COOR, lead tetracylate and the aryl iodosoacylate may COCOOR or COCN is introduced into suitably be caused to act in about molecular prothe alkyl group adjacent to the side chain carportions, in organic solvents indifierent against bonyl, the products obtained by the reaction are said agents.

subjected, if required after the transformation by 5 The reaction occurs according to the following saponifying agents and/or agents splitting off CO scheme:

CH3 CH3 CH3 om CH3 \-(|J=O -cmoocoon l l i H l COOR l saponification CH1 CH3 CH3 CH3 -(||JOHz-CO o R -(HJOH2C 0-0 0 OH I l HO oxidation HO i lead tetraacetate or l aryl-iodosoacetate CH3 CH3 CH3 CH3 OCHC o o R A -oornon I 1" I t V 00 saponification V (1:113 and 002- HO cleavage HO- Pregnendiol-(3,21)-on-(20) is complete, to oxidizing agents rendering possi The ketones free from hydroxy may be conble the introduction of a free or substituted hydensed with the same or a similar success with droxyl group into the alkyl group carrying the ethyl acetate, chlorocarbonic acid ester, cyanocarbonic acid ester and other suitable substances allowing the introduction of an acid radical into the alkyl group, and a free or an esterified hydroxyl group may be introduced into the products obtained by the reactionand the Whole may be further treated accordingly. By replacing for instance a hydrogen atom of the alkyl group adjacent to the carbonyl group'by'an alkali me'tal and condensing the alkali metal compound obtained with chlorocarbcnic acid ester, the condensation product may be worked up in the manner described above.

If it is intended to transform a hydroxyl group which may stand in 3-position simultaneously into the keto group, said step of the process may be carried through in known manner, for instance with sodium butylate in the presence of acetone, directly before or after the treatment with lead tetracylates or aryl iodosoacylates.

The following example serves to illustrate the invention, but it is not intended to limit it thereto 6.32 grams of pregnenol-(3)-on-(20) and 5.84 grams of oxalic acid diethyl ester (freshly distilled) or the corresponding quantity of dimethylester, dipropylester or dibutylester are added to -a sodium alcoholate solution prepared from 0.6

ram of sodium and 65 cc. of absolute alcohol and the solution thus obtained is heated for 6 hours in a reflux apparatus. After a short time a dense precipitate already separates. After having boiled for 6 hours the solution is saponified for 45 minutes with 100 grams of ethylalcoholic potash lye of 5 per cent strength, the mixture is poured into water acidified With sulfuric acid and shaken out with ether. By the addition of a smallquantity of ethyl acetate the dissolution in ether of the precipitate separated in flakes is accelerated. The acid formed is removed from the solution of ether and ethyl acetate by means of a sodium carbonate solution, the sodium salt is centrifuged, decomposed with dilute sulfuric acid and taken up again with ethyl acetate. The ethyl acetate solution is dried and evaporated and the residue is redissolved in methanol. The product melts at 225 C. with decomposition; it corresponds to the empirical formula; C23H32O5 and has the following structural formula:

CH3 CH3 194 milligrams of pregnenol-(dii-(20l-cai boxylic acid ethyl ester (21) and 245 milligrams oflead tetracetate in 30 cc. of benzene free from thiophen are kept for 6 hours at C. 0., While stirring; the solution is then filtered, the

, clear solution is washed with water and after drop by drop within the course of 15 minutes,

leum ether solutionthe pregnenol-(3)-on-.(20)- V carboxylic acid ethyl ester-(21) crystallizes. The melting point of the product is at 99 C. (uncorrected). 7

having been dried over sodium sulfate it is evaporated. .,The' residue very strongly reduces am- 'moniacal silver salt solution. It is dissolved in 12.5 cc. of alcohol of 96 per cent strength and the solution is heated for 1 hour in a reflux apparatus together with 9.5 cc. of water and 0.5 cc.

of concentrated sulfuric acid. The solution is poured into water, the aqueous mixture is extracted with ether and the residue of the ether is distilled under highly reduced pressure: The boiling point of the product amounts up to 210 C. under a pressure of 0.02 mm. The pregnendiol-(3.2l) on-(ZO) is isolated from the partly crystallized distillate.

We claim:

1. The process which comprises condensing a diester of oxalic acid with a pregnenolone, sa-

' ing the free acid by means of an agent of the group consisting of lead tetraacylates and aryl iodosoacylates in an organic solvent inert against said oxidizing agents and in the presence of an alcohol, causing an agent of the group consisting of lead tetraacylates and aryl iodosoacylates to act upon the pregnenol-(3) one-(20) carboxylic acid ester-(21) thus obtained, saponifying the reaction product and eliminating carbon dioxide from the free acid.

3. The process which comprises condensing .a diester of oxalic acid with pregnenol-(3) one- (20) saponifying the ester thus obtained, oxidizing the free acid by means of about 1 mol of an agent of the group consisting of lead tetraacylates and aryl iodosoacylates in an organic solvent inert against said oxidizing agents and in the presence of ethyl alcohol, causing about 1 mol of an agent of the group consisting of lead tetraacylates and aryliodosoacylates to act upon the pregnenol-(3)-one-(20) carboxylic acid ester- (21) thus obtained, saponifying the reaction product and eliminating carbon dioxide from the free acid.

4. The product of the following formula:

CH3 CH MAX BooKMiiHL. GUSTAV EHRHART. HEINRICH RUSCHIG. 

